PROJECT SUMMARY Patients with ocular anterior segment dysgenesis (ASD) have a greatly elevated risk of developing severe, early onset glaucoma that is refractory to treatment. Between 50-75% of patients with ASD develop glaucoma, which occurs at significantly younger ages than in the general population, leading to disproportionately diminished quality of life for patients and their families. We propose that intrinsic vascular defects are a primary insult contributing to ASD that are distinct from defects in periocular mesenchyme differentiation. We will test this hypothesis using highly advanced ultramicroscopy, innovative cell-labeling approaches, state-of-the-art nanofluidics technologies and unique and complementary genetic resources. This etiological distinction between migration and differentiation may have significant implications for patient stratification with respect to prognosis, management of modifiable risk factors and awareness of potentially life-threatening co-morbidities ? all of which are important for genetic counseling, family planning and patients' psychological well being.